• MITOCHONDRIAL ELECTRON TRANSPORT CHAIN ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS

      Perl, Andras; Doherty, Edward (2014)
      Systemic lupus erythematosus (SLE) is an autoimmune disorder, characterized by T cell and B cell dysfunction. SLE mitochondria have been shown to be dysfunctional with increased mass, mitochondrial potential, decreased ATP, elevated reactive oxygen species (ROS) and reactive nitrogen species (RNS) concentrations, and altered Ca2+ stores. Drug treatments that target the mitochondria have shown efficacy in treating SLE. Here we have investigated electron transport chain (ETC) activity in SLE, to better understand the causes of mitochondrial dysfunction in SLE. We have found that mitochondrial complexes I and IV of the ETC have elevated respiration in SLE compared to healthy controls after both overnight resting and anti-CD3/CD28 stimulation. We have also shown that SLE complex I is resistant to NO inhibition of respiration. SLE peripheral blood lymphocytes (PBL) have increased S-nitrosylation (SNO) while immunoprecipitated complex I had decreased SNO of proteins compared to healthy controls. The drug Nacetylcysteine (NAC) was able to inhibit complex I activity in SLE, and was found to reduce the amount of complex I protein NDUFS3 after 15 minutes as measured by western blotting. These results have led us to the conclusion that SLE mitochondrial complex I is in an active form which is resistant to SNO and is driving the production of ROS and RNS that are associated with SLE. The drug NAC is able to inhibit complex I respiration which may have therapeutic efficacy by reducing the ROS and RNS stress in SLE.
    • MITOCHONDRIAL PROTEINS AS TUMOR MARKERS AND ANTI-CANCER DRUG TARGETS

      Sheikh, Saeed; Babbar, Mansi (2017)
      Cancer is a major cause of morbidity and mortality. Identification and characterization of novel biomarkers are expected to facilitate early diagnosis and improve prognosis of human malignancies. Increasing number of studies have linked tumor progression with metabolic reprogramming. However, the players involved are not fully discovered. Therefore, understanding the cancer cell plasticity may offer a successful approach for an anti-cancer strategy. In this regard, we report the functional characterization of Coiled-coil Helix Tumor and Metabolism 1 (CHTM1) and KM1 as important regulator of cancer cell metabolism.CHTM1 is localized in cytosol and mitochondrial inter-membrane spaceand regulates mitochondrial activity. Our results demonstrate that MIA40 appears to alterCHTM1 mitochondrial localizationand stability. Further, CHTM1 cysteineresiduesinvolved in CHTM1 folding modulatescellular distributionof CHTM1. Importantly, alterations in CHTM1 expression in cancer cells affect mitochondrial activity. Given thatmitochondria play an important role in cellular response to nutrient stress, we sought to analyze the role of CHTM1 in glucose/glutamine-deprived conditions. Wehave found thatCHTM1 deficiency enhancescancer cell sensitivityto glucose/glutamine starvation and metformin treatment. Additionally, increased sensitivity of CHTM1-deficient cells to metabolic stress could be in part due to inability to activate fatty acid oxidation. Further, targeting CHTM1 expression in cancer cells reduce fatty acid oxidation causing decrease in substrate availability under metabolic stress conditions. This can explain the increase in autophagy and protein catabolism in CHTM1-deficient cancer cells under metabolic stress conditions. Mechanistic studies suggest that CHTM1-mediated alterations in cancer cell metabolism under stress conditions involve modulation of PGC1 alpha-CREB-PKC signaling.We further demonstrate that under metabolic stress, CHTM1 deficiency activates p38-AIF1pathway leading to increased cell death. CHTM1 negatively regulates p38 and interacts with AIF1 alteringAIF1release frommitochondria under metabolic stress conditions.These findings are highly significant because alterations in cancer cell metabolism are linked to pathogenesis of cancer. Most importantly, multiple human malignancies associated with breast, colon and lung tissuesshow increase in CHTM1 expression. CHTM1 appears to be a high value tumor marker, that has the potential tofacilitate earlydiagnosis of human malignancies and could also serve as a target to develop novel therapeutics to manage human malignancies. In the second part of this manuscript, we report the characterization of a novel protein temporarily named as KM1. Our results indicate that KM1 is localized inthemitochondrial inner membrane and regulates mitochondrial activity. Metabolic stress-induced increased cell death is noted in KM1 knockout cancer cells, a finding consistent with the defective mitochondria in KM1-deficient cells. Our results further demonstrate that under metabolic stress KM1 regulates mitochondrial-mediated cell death. Most importantly, KM1 levels are upregulated in breast and lung cancer tissues.Collectively, our results suggest that CHTM1 and KM1 are novel proteins and are involved in regulating cancer cell metabolism.
    • A Mobile Application for a Growing Utica Comets Community

      MacIntosh, Jessica; Kahn, Russel; Adviser; Schneider, Steven; Reviewer (2016-05-01)
      This research project is a prototype of a mobile application that would be dedicated to the Utica Comet hockey community and its team through the use of special fan features to give the area a sense of belonging. The development of this application uses the human-centered design theory as well a hierarchy of needs, which were incorporated into the design of the app. The mobile app was created using a web design program within the Adobe Creative Suite. This research paper looks into the need to clarify the concepts of community, belonging and social identification within the sport of hockey. As the target users, their needs and wants are determined. It then details the concepts of creating an app, which are assessed and applied to the prototype.
    • Mobile Strategy Plan for Higher Education

      DeFranco, Tony (2011-08-01)
      The study investigates what is involved in the development of a mobile strategy for a college. In addressing this question, the thesis contains three parts. First, was a request for proposal (RFP); next, was a consultant’s proposal in response to the RFP; and the third part was an evaluative document explaining and reflecting on the writing process. There are four key issues in developing a mobile strategy. The first issue is to create a device-agnostic mobile framework capable of supporting multiple mobile platforms. Next is focusing on building mobile applications that take advantage of device-specific features on the vast majority of devices. The third issue is facilitating a consistent mobile identity with one outward presence comprised of links to essential college information systems. Finally, developers must conform to mobile Web standards such as W3C Mobile Web Best Practices
    • Mobile technologies aide cancer patients in rural areas with digital medicine to seek a second opinion

      Wurz, Stacy L (2015-12)
      This mobile application provides cancer patients in rural areas the ability to seek a second opinion from more experienced physicians based on the criteria they input. According to the N.Y. Times there are over 100,000 medical mobile applications, (Krisch, pg. 1) however none that are listed provide a second opinion. Through research and by observing the needs of cancer patients in rural areas, the need for mobile Internet technology is great as rural areas lack connectivity of high-speed PC-based Internet access to access proper medical needs. This application breaks the digital divide by introducing a mobile platform to seek more experienced physicians who can offer a second opinion. It has been designed on a platform of a hierarchy of needs which guides the user through menus situated in two areas of the application. The design features an aesthetic light blue warm hue, which is inviting to the user. Once the user registers for the application, they are free to engage with others through a forum and ultimately design and implement their own health-care plan.
    • Modern Virtual Environments and Museums

      Stam, Kathryn; Thesis Advisor; Lizardi, Ryan; Ewsuk, Christopher (2020-10)
      Today, many places and environments are replicated digitally for several different reasons. Some of these popular use-cases include video-games, virtual travel, remote learning, and virtual museums. In some cases, they are purely for entertainment, and in others they are purely for convenience or reaching a wider audience. Digital museums, virtual tours, and even modern video games replicate actual and historical places into “Virtual Worlds” in order to overcome barriers like distance, travel, cost, availability, and even existence. Through studying various literature, case studies, and deployed applications, this project will attempt to understand the history and development of virtual worlds and how we use them today. Using the popular example of Virtual Museums, this paper and the associated project attempt to explore and analyze the value and quality of learning and process involved in the deployment of a virtual world.
    • Molecular Analysisof Saccharomyc escerevisiae RNA Polymerase I Core Factor Complex and its Interaction with Promoter DNA

      Knutson, Bruce; Jackobel, Ashleigh J (2020)
      Gene transcription and protein synthesis are essential molecular processes required for all living organisms. In eukaryotes, messages encoded within DNA are transcribed by three DNA-dependent RNA polymerases (Pols I-III) into ribosomal RNA (rRNA), messenger RNA (mRNA), and transfer RNA (tRNA), respectively. General transcription factors (GTFs) help recruit Pols to their appropriate gene promoters as well as facilitate template opening and transcription start site (TSS) selection. In Saccharomyces cerevisiae, the Pol I pre-initiation complex (PIC) is formed by numerous GTFs that include Upstream Activating Factor (UAF), Core Factor (CF), TATA-binding protein (TBP), and Rrn3. This unique set of GTFs engage ribosomal DNA (rDNA) through interactions with regulatory elements of the promoter known as the Upstream Activating Sequence (UAS) and the Core Element (CE). Here, we resolve the cryo-electron microscopy (cryo-EM) structure of CF bound to the rDNA promoter at 3.8Å near-atomic resolution and determine itsDNA binding preferences in which CF preferentially binds to the GC-minor groove. Briefly, our cryo-EM studies reveal that the CF-DNA interaction is mediated by two CF subunits, Rrn7 and Rrn11. We also found that the path of promoter DNA is relatively straight in the Pol I PIC, which is strikingly different from the bent promoters observed in structures of the Pols II/III PICs. We identified three states of CF engagement with promoter DNA (States 1-3) in which CF acts as a ratchet toforceDNA into the active site of the polymerase that facilitates the melting of the double-stranded DNA template in an ATP-independent manner, another unique feature of the Pol I system. Using in vitroDNA binding assays, we have identified a 12 base pair (bp) region within the CE that is necessary and sufficient for CF binding. We have also demonstrated that the human anticancer compound CX-5461 can inhibit yeast cell growth and blocks yeast CF binding to both yeast and human rDNA promoters in vitro. Furthermore, we show that the human Core Promoter Element (CPE) can functionally replace the yeast CE in a position-dependent manner. Together, these results reveal the unique molecular architecture of the Pol I PIC and suggest a conserved sequence-independent binding mechanism of CF with promoter DNA.
    • The monoamine oxidase B gene exhibits significant association to ADHD

      Li, Jun; Wang, Yufeng; Hu, Songnian; Zhou, Rulun; Yu, Xiaomin; Wang, Bing; Guan, Lili; Yang, Li; Zhang, Feng; Faraone, Stephen V. (Wiley, 2008)
      Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition with strong genetic basis. Recent work in China indicated that ADHD may be linked to Xp1–2 in the Han Chinese population. The gene encoding monoamine oxidase B (MAOB), the main enzyme degrading dopamine in the human brain, is located in this region. The current study sequenced the exons and the 50 and 30 flanking regions of theMAOBgene and found four common variants including 2276C>T and 2327C>T in exon 15, rs1799836 in intron 13 and rs1040399 in 30-UTR. We assessed the association of these variants with ADHD in 548 trios collected from 468 males and 80 females probands. TDT analysis showed that alleles of each polymorphism were preferentially transmitted to probands (rs1799836, P¼3.28E-15; rs1040399, P¼1.87E-6; 2276T>C or 2327T>C, P¼2.20E-6) and haplotype-based TDT analyses also found distorted transmission. In conclusion, this study provides the strongest evidence for the involvement of MAOB gene in the etiology of ADHD to date, at least in Han Chinese population.
    • The Motivational Effects of Using a Computer-Based Tutorial vs. a Traditional Instruction Method for Learning How to Use an Elementary Level Mathematics Game

      Roth, Christopher (2012-05-01)
      The purpose of this project was to develop and evaluate a computer-based tutorial to educate students on how to use an elementary level mathematics game. The emphasis of the tool was based on the cognitive learning principle of motivation, as described in Malone's motivation theory. The research explored the motivational effects of using the tutorial versus a traditional learning method, advantages and disadvantages to teachers and students, and improvements that could enhance the learning process. This qualitative case study employed post-testing, interviews, and referenced literary resources to collect and analyze data. Tutorial users scored ten percent higher on the post-test than the instruction sheet users. Advantages of the tutorial included user control, visual references, and assistance for learning disabilities. Disadvantages included loss of human interaction and the preparation and development process. Character development (fantasy), increased audio/video combinations, and more challenging elements were cited as areas for increasing motivation.
    • MULTI-FUNCTIONAL EFFECTOR RESPONSES ELICITED FROM IgM MEMORY STEM CELLS

      Winslow, Gary; Kenderes, Kevin (2017)
      The response of memory B cells to challenge infection is fundamental to longterm protection against pathogens. Following challenge, memory B cells can rapidly differentiate into antibody-secreting cells (ASCs) to produce a secondary antibody response. Memory B cells have also been shown to re-enter into germinal centers and undergo additional rounds of affinity maturation. Both the isotype of the B cell and the signals that generated the B cell have been proposed to modulate how memory B cells respond. Initial studies proposed BCR-intrinsic factors are responsible for the differentiation of memory cells. IgM memory cells undergo differentiation in GCs following antigen challenge, while IgG memory cells rapidly differentiate into ASCs. Other studies found no link-between BCR isotype and differentiation. We investigated the differentiation of T-bet+ CD11c+ IgM memory B cells following challenge infection. IgM memory cells differentiated into IgM-producing plasmablasts. Other IgM memory B cells entered germinal centers, underwent class switching, and became switched memory cells. Yet other donor cells were maintained as IgM memory cells. The IgM memory cells also retained their multi-lineage potential following serial transfer. The kinetics of the IgM memory response mimicked the kinetics of the primary response. Thus, IgM memory cells can differentiate into all effector B cell lineages, and undergo self-renewal, properties that are characteristic of stem cells; however, differentiation occurs with the same kinetics of the primary response. We propose that memory B cells have varying degrees of stem cell likeness. IgM memory stem cells retain the most differentiating capacity but respond to challenge similarly to naïve cells, while IgG effector memory cells are primed to rapidly differentiate into IgG ASCs.
    • The multidimensionality of schizotypy in nonpsychotic relatives of patients with schizophrenia and its applications in ordered subsets linkage analysis of schizophrenia

      Lien, Yin-Ju; Tsuang, Hui-Chun; Chiang, Abigail; Liu, Chih-Min; Hsieh, Ming H.; Hwang, Tzung-Jeng; Liu, Shi K.; Hsiao, Po-Chang; Faraone, Stephen V.; Tsuang, Ming T.; et al. (Wiley, 2009)
      This study aimed to examine the multidimensionality of schizotypy and validate the structure using ordered subset linkage analyses on information from both relatives’ schizotypy and probands’ schizophrenia symptoms. A total of 203 and 1,310 nonpsychotic first-degree relatives from simplex and multiplex schizophrenia families, respectively, were interviewed with the Diagnostic Interview for Genetic Studies, which contains a modified Structured Interview for Schizotypy. Using Mplus program with categorical factor indicators, a four-factor model (Negative Schizotypy, Positive Schizotypy, Interpersonal Sensitivity, and Social Isolation/Introversion) was extracted by exploratory factor analysis from relatives of simplex families and was confirmed in relatives of multiplex families. The validity of each factor was supported by distinct linkage findings resulting from ordered subset analysis based on different combinations of schizophrenia–schizotypy factors. Six chromosomal regions with significant increase in nonparametric linkage z score (NPL-Z) were found as follows: 15q21.1 (NPLZ ¼3.60) for Negative Schizophrenia–Negative Schizotypy, 10q22.3 (NPL-Z¼3.83) and 15q21.3 (NPL-Z¼3.36) for Negative Schizophrenia–Social Isolation/Introversion, 5q14.2 (NPL-Z¼3.20) and 11q23.3 (NPL-Z¼3.31) for Positive Schizophrenia–Positive Schizotypy, and 4q32.1 (NPL-Z¼3.31- ) for Positive Schizophrenia–Interpersonal Sensitivity. The greatest NPL-Z of 3.83 on 10q22.3 in the subset was significantly higher than the greatest one of 2.88 in the whole sample (empirical P-value¼0.04). We concluded that a consistent four-factor model of schizotypy could be derived in nonpsychotic relatives across families of patients with different genetic loadings in schizophrenia. Their differential relations to linkage signals have etiological implications and provide further evidence for their validity. 2009 Wiley-Liss, Inc.
    • Nanoscale Schottky Barrier Visualization Utilizing Computational Modeling and Ballistic Electron Emission Microscopy

      Nolting, Westly; LaBella, Vincent; Advisor (2018-05)
      Understanding the properties and performance of semiconductor interfaces on the nanoscale advances semiconductor device technology which has had tremendous impact on nearly all aspects of our daily lives. Investigating the nanoscale fluctuations in the electrostatics of metal-semiconductor, or Schottky, interfaces is crucial. However, techniques for directly measuring the electrostatics at an interface are limited. Current state-of-the-art finFETs use metal-semiconductor silicides, such as Ti-Si/Si, for Schottky source-drain contacts. Studying the underlying physics of the Schottky barrier interface of silicides and other metal-semiconductor systems is critical for measuring the Schottky barrier accurately, which can be accomplished with ballistic electron emission microscopy (BEEM), a scanning tunneling microscopy (STM) based technique. In this work, the visualization of the interface to nanoscale dimensions is enhanced by computational modelling of threshold histograms acquired by the BEEM measurement technique. Modelling using a kinetic Monte-Carlo approach is utilized to simulate the distributions of barrier heights that includes effects from the interface and transport of the hot electrons as well as indication of a multi-barrier heights present at the interface. The aid of this modelling enables the discovery of several underlying properties of the interface. Analyzing the parameters of the modelling and comparing to measured data provides detailed insight into the effects that both electron scattering and incomplete silicide formation in W/Si(001) and WSi2/Si(001) have upon the transport of electrons through these structures, which is difficult to detect with conventional current-voltage measurements. The modelling also includes simulation of multiple barriers present at the interface due to the intermixing of similar metals such as Au and Ag at the interface of Si(001) In this regard, Schottky barrier visualization as the combination of histograms, mapping, and modelling provides a new insight into the local nanoscale phenomenon of the Schottky barrier. This thesis investigates the modelling of these metal-semiconductor systems and uses modelling to look at metal thickness dependent effects on the Schottky barrier from Fermi-level pinning in Au/Cr-Si/Si(001) and Au/Cr-Si/Si(111) silicide.
    • NautiCode: Coding for Kids

      Zeo, Brittany; Mullick, Rosemary; Adviser; Sarner, Ronald; Reviewer; Urban, Christopher; Reviewer (2016-05-08)
      Throughout my college career, I have asked students what made them decide to major in Computer Science. The answers I received very seldom revealed previous coding experience. Unfortunately, this is the system: you don’t know what you want to major in and so you choose something that looks interesting. You just hope it works out for the best. Fortunately for me, I had four years of programming experience in classes before reaching college as well as being a programmer on my high school’s FIRST Robotics team. This previous exposure to coding allowed me to make an educated decision about what I wanted to major in. It is not always the case that an individual gets this experience, and I want to change that. For my Masters Project, I have decided to come up with a website to get kids to learn and practice some basic concepts of coding: NautiCode. My target audience is mid to upper elementary school children. And best of all, there is no previous coding experience needed when using NautiCode. Even if Computer Science is not their career choice, they can have the exposure at an early age. Coding does not only benefit computer scientists; just having the background knowledge of concepts such as: logic, data storage, and how things relate, can be beneficial to an individual for any major. These ideas can help individuals think about problems differently and come up with solutions that would not have been possible had they not been exposed to computer science concepts. What better time in an individual’s life to introduce these concepts than childhood. Children’s brains are magnificent. They can absorb so much information and they think differently about the world. This leads to creative solutions and a new perspective. What I aim to do with NautiCode is to get children thinking in new ways and exploit their creativity and spark new ideas. I aim to give an explanation of the simple concepts in an introduction and gradually work up towards more difficult problems. Children are more capable than they know and with a little guidance, they can start creating their own technologies in no time. NautiCode is a fully functional website that I created on my own. The front end is using Scss, and HTML5 while the backend is using PHP, SQL, JS, and AJAX. My databases are being hosted locally through phpMyAdmin and MAMP.
    • NEAR-ATOMIC RESOLUTION STRUCTURE OF THE YEAST VACUOLAR (V-) ATPASE MEMBRANE SECTOR Vo IN LIPID NANODISC

      Wilkens, Stephan; Stam, Nicholas J (2020-04-10)
      Vacuolar ATPase (V-ATPase) is a large multisubunit enzyme that acidifies subcellular organelles and the extracellular space. Its activity is regulated by reversible disassembly, causing V-ATPase dissociation into soluble V1-ATPase and membrane-integral Voproton channel sectors.The goal of this thesis project was to observethe yeast Voin a physiologically relevant, auto-inhibited state, i.e. in its form dissociated from the ATPase sector, V1, in order to better visualizethe closed pore and to identify testable hypotheses on why the pore remains closed following dissociation from V1. Towards this aim we present two chapters:In Chapter 1, we detail a single-particle negative stain EM study of lipid nanodisc reconstituted Vo,which suggesteddissociated Vois halted in theso-called rotational state 3 of the holo-enzyme.We performed site directed mutagenesis and binding studies of subunits aand dto test and validate this hypothesis.In Chapter 2,we further detaillipid nanodisc reconstitutedVoin a high-resolutioncryoEM structure,confirmingour earlier identification of Voresting in rotational state 3, andproviding structural information of the sectorat the amino acid level. Through this work we proposed apossible mechanism for transmembrane proton transport in the V-ATPaseandidentifieda new subunit member of Vo, assembly factor Voa1.The studies shown here highlight the potential of lipid nanodisc reconstitution of membrane protein complexes, give insight into a conformational mismatch between autoinhibited V1and halted Vowith the implication that the mismatch may serve to prevent unintended reassembly of V-ATPase upon activity silencing, and propose a chemical basis for transmembrane proton transport in the Voproton pore.
    • Nearwork-Induced Transient Myopia (NITM) Following Marked and Sustained, but Interrupted, Accommodation at Near

      Arunthavaraja, Mathangi (2010-07-16)
      Purpose: It has been speculated that non-decayed NITM (accommodatively-based nearwork-induced transient myopia) may be myopigenic in nature. Thus, the purpose of the present investigation was to determine objectively the initial magnitude and decay of NITM, and its potential additivity, following successive but interrupted periods of marked, sustained accommodation at near in asymptomatic young-adult myopic subjects. Methods: Fifteen visually-normal, asymptomatic young adults (ages 18 – 28 years) were tested with full distance refractive correction. They included 9 early-onset (EOM) and 6 late-onset (LOM) myopic subjects. Accommodation was assessed objectively with a Canon R-1, open-field, infrared auto-refractor under monocular viewing conditions (RE). The distance refractive state was measured immediately before and after a ten minute period of focusing upon a moderate contrast (50%), very near target (12 cm; 8D) subtending a visual angle of 1 degree. The task was repeated twice with a 5-minute inter-task rest period of imposed far viewing. NITM was defined as the post-task minus pre-task change in distance refractive state immediately following each task. Results: Significant amounts of NITM were generated following nearly each trial in each subject. These ranged from 0.11 to 0.71D, with a mean of 0.31D. The group mean NITM was 0.32, 0.29, and 0.31D for trials 1, 2, and 3, respectively. For the EOMs subgroup, NITM was 0.28, 0.30, and 0.34D, while for the LOMs subgroup, it was 0.38, 0.29, and 0.26D, for for trials 1, 2, and 3, respectively. Decay of NITM was prolonged in many of the subjects (67%). However, additivity of NITM was not found following the sequences of interrupted near tasks. Conclusions: There was no evidence of NITM additivity following a marked and sustained, but interrupted, near task. Although NITM has been reported to be additive following long periods of uninterrupted and sustained reading at lower dioptric levels, providing rest periods between each near task trial appears to prevent a cumulative effect (i.e., additivity effect). These findings support the idea of far viewing being protective in nature from myopia development.
    • Neuropsychological intra-individual variability explains unique genetic variance of ADHD and shows suggestive linkage to chromosomes 12, 13, and 17

      Frazier-Wood, Alexis C.; Bralten, Janita; Arias-Vasquez, Alejandro; Luman, Marjolein; Ooterlaan, Jaap; Sergeant, Joseph; Faraone, Stephen V.; Buitelaar, Jan; Franke, Barbara; Kuntsi, Jonna; et al. (Wiley, 2012-01-05)
      Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric disorder that is usually accompanied by neuropsychological impairments. The use of heritable, psychometrically robust traits that show association with the disorder of interest can increase the power of gene-finding studies. Due to the robust association of intra-individual variability with ADHD on a phenotypic and genetic level, intra-individual variability is a prime candidate for such an attempt. We aimed to combine intra-individual variability measures across tasks into one more heritable measure, to examine the relatedness to other cognitive factors, and to explore the genetic underpinnings through quantitative trait linkage analysis. Intra-individual variability measures from seven tasks were available for 238 ADHD families (350 ADHD-affected and 195 non-affected children) and 147 control families (271 children). Intra-individual variability measures from seven different tasks shared common variance and could be used to construct an aggregated measure. This aggregated measure was largely independent from other cognitive factors related to ADHD and showed suggestive linkage to chromosomes 12q24.3 (LOD ¼ 2.93), 13q22.2 (LOD ¼ 2.36), and 17p13.3 (LOD ¼ 2.00). A common intra-individual variability construct can be extracted from very diverse neuropsychological tasks; this construct taps into unique genetic aspects of ADHD and may relate to loci conferring risk for ADHD (12q24.3 and 17p13.3) and possibly autism (12q24.3). Given that joining of data across sites boosts the power for genetic analyses, our findings are promising in showing that intra-individual variability measures are viable candidates for across site analyses where different tasks have been used.
    • The new neuropsychiatric genetics

      Faraone, Stephen V.; Smoller, J.W.; Pato, C.N.; Sullivan, P.; Tsuang, M.T. (Wiley, 2008-01-05)
    • New Techniques for Public Key Encryption with Sender Recovery

      Godi, Murali; Viswanathan, Roopa; Adviser; Novillo, Jorge; Reviewer; Chiang, Chen-Fu; Reviewer (2016-12-15)
      In this paper, we consider a situation where a sender transmits a ciphertext to a receiver using a public-key encryption scheme, and at a later point of time, wants to retrieve the plaintext, without having to request the receiver’s help in decrypting the ciphertext, and without having to store a set of plaintext/ciphertext pairs for every receiver the sender interacts with. This problem, known as public key encryption with sender recovery has intuitive solutions based on KEM/DEM schemes. We propose a KEM/DEM-based solution that is CCA-secure, and only requires the receiver to be equipped with a public/secret key pair (the sender needs only a symmetric recovery key), and has much simplified proofs compared to prior work in this area. We prove our protocols secure in the single receiver and multi-receiver setting. To achieve our goals, we use an analysis technique called plaintext randomization that results in greatly simplified and intuitive proofs for protocols that use a PKE internally as a component and compose the PKE with other primitives. We instantiate our protocol for public key encryption with sender recovery with the well-known KEM/DEM scheme due to Cramer and Shoup.